Hyperglycemia is a common disease that afflicts the adult population in developed countries. Hyperglycemia type I, e.g., insulin-dependent diabetes, can be treated by insulin administration, but more than 90% of hyperglycemia patients suffer from insulin-independent hyperglycemia for which insulin treatment is not effective. Although many drugs have been developed for insulin-independent hyperglycemia patients, they are still ineffective and relatively toxic.
The present inventors have endeavored to develop a non-toxic drug having improved efficacy in lowering the blood glucose level; and have unexpectedly discovered that bioflavonoids exhibit excellent blood glucose level lowering effects.
Hitherto, citrus peel has been discarded or used only for the preparation of an animal fodder or organic fertilizer. Dried citrus peel comprises 50 to 60 wt % of alcohol-insoluble polymers such as pectin, hemicellulose and cellulose; 30 to 50 wt % of alcohol-soluble solid materials(80 wt % thereof consisting of glucose, fructose and sucrose); and small amounts of bioflavonoids, vitamins, limonoids, phenolic compounds and oils. In particular, various bioflavonoids, such as those listed in Table I, are present in the citrus peel(Horowitz, R. M., et al., J. Org. Chem., 25, 2183-2187(1960)). Hesperidin is the major bioflavonoid component found in orange, lemon and tangerine; naringin represents the major bioflavonoid component in grapefruit; and naringin and hesperidin are present in citron in nearly equal amounts.
TABLE I ______________________________________ Citrus fruit Bioflavonoids ______________________________________ Grapefruit apigenin, dihydrokaempferol, eriodictyol, hesperetin, hesperidin, isorhamnetin, isosakuranetin, kaempferol, naringenin, naringin, neohesperidin, poncirin, quercetin, rutin Lemon apigenin, apigenin 7-rutinoside, chrysoeriol, diosmin, eriocitrin, hesperidin, isorhamnetin, limocitrin, limocitrol, luteolin 7-rutinoside, naringin, neohesperidin, poncirin, quercetin Orange auranetin, hesperidin, isosakuranetin 7- rutinoside, naringin, neohesperidin, nobiletin, rutin, sinensetin, tangeretin, vitexin Tangerine hesperidin, nobiletin, tangeretin ______________________________________
It has been reported that the bioflavonoids isolated from citrus peel have anti-oxidative, anti-cancer, anti-viral and blood-pressure lowering activities(Saija, A., et al., Free Radical Biol. Med., 19, 481-486(1995); Matsubara, Y., et al., Japan Organic Synthesis Chem. Association Journal, 52, 318-327(1994, Mar.); Galati, E. M., et al., Farmaco., 51(3), 219-221(1996, Mar.); Felicia, V., et al., Nutr. Cancer, 26, 167-181(1996); EP 0352147 A2(1990. 1. 24); and Kaul, T. N., et al., J. Med. Viol., 15, 71-75(1985)).
However, bioflavonoids have never been reported to have blood glucose level lowering activity.